Integrated PhD Biomedical Science

生物医学综合博士

• 批准号: 2880816
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2880816
• 关键词: Integrated; PhD; Biomedical; Science

Alzheimer's disease (AD) is a progressive condition in the brain whereby there is accumulation of misfolded proteins, leading to the loss of neurons and their connections. Many genes associated with the risk of developing AD are implicated in microglial function. Microglia are immune cells which reside in the brain and are responsible for the clearance of harmful stimuli. In AD, they are activated for sustained periods which can lead to chronic neuroinflammation and contribute to disease pathology. When investigating microglial genes, the SLC family was identified as having a very high predictive value for AD development. This family of proteins has been shown to be important for coordinating immune responses and regulating inflammation systemically, suggesting that the gene may play a role in the immune response in the brain by regulating microglial function. In this project, we will compare the expression of genes from the SLC family in non-diseased and AD human brains using published databases, while investigating other genes belonging to the same gene family with similar functions. We will also use human tissue to confirm that these proteins are expressed in microglial cells. Subsequently, we will use human cells which can be differentiated into microglial-like cells to create a cellular model which mimics the presence of misfolded proteins. Then we will induce gene knockouts to study the function of our genes of interest in a human AD model. Hence, we will characterise expression and function of these genes to understand how the genetic variants may contribute to chronic neuroinflammation and AD pathology.

阿尔茨海默病（AD）是一种大脑中的进行性病症，其中存在错误折叠的蛋白质的积累，导致神经元及其连接的丧失。许多与发展AD风险相关的基因与小胶质细胞功能有关。小胶质细胞是存在于大脑中的免疫细胞，负责清除有害刺激。在AD中，它们被持续激活，这可能导致慢性神经炎症并导致疾病病理学。当研究小胶质细胞基因时，SLC家族被鉴定为对AD发展具有非常高的预测价值。该蛋白质家族已被证明对于协调免疫反应和全身调节炎症非常重要，这表明该基因可能通过调节小胶质细胞功能在大脑中的免疫反应中发挥作用。在这个项目中，我们将使用已发表的数据库比较SLC家族基因在非疾病和AD人脑中的表达，同时研究属于同一基因家族的具有相似功能的其他基因。我们还将使用人体组织来证实这些蛋白质在小胶质细胞中表达。随后，我们将使用可以分化为小胶质细胞样细胞的人类细胞来创建模拟错误折叠蛋白质存在的细胞模型。然后我们将诱导基因敲除，以研究我们感兴趣的基因在人类AD模型中的功能。因此，我们将研究这些基因的表达和功能，以了解遗传变异如何导致慢性神经炎症和AD病理。